Properdin binds to sulfatide [Gal(3-SO4)beta 1-1 Cer] and has a sequence homology with other proteins that bind sulfated glycoconjugates.
Properdin, which stabilizes the C3 convertase during the activation of the alternate complement pathway, contains amino acid sequence homologies with several proteins that bind sulfated glycoconjugates, including the adhesive protein thrombospondin and the leech salivary protein antistasin. This homology is based around the sequence Cys-Ser-Val-Thr-Cys-Gly-X-Gly-X-X-X-Arg-X-Arg. To determine if these homologous amino acid sequences are sulfated glycoconjugate-binding domains, purified native properdin, as well as activated properdin (a high molecular weight form of properdin), were examined for binding to various lipids in solid phase radioimmunoassays. Of the lipids tested, both native and activated properdin bind with high affinity only to sulfatide [Gal(3-SO4)beta 1-1 Cer], but not to comparable levels of cholesterol-3-SO4, or several neutral glycolipids, gangliosides, and phospholipids. Sulfatide binding by both forms of properdin is inhibited by dextran sulfate (Mr = 500,000) or fucoidan, whereas only the activated form is inhibited by dextran sulfate (Mr = 5,000) or heparin. Comparable levels of chondroitin sulfates A, B, and C, keratan sulfate, dextran (Mr = 90,000), or hyaluronic acid do not inhibit binding. Taken together, these data suggest that properdin, like antistasin and thrombospondin, binds sulfated glycoconjugates and supports the conclusion that the homologous sequences are sulfated glycoconjugate-binding domains.
Holt
G D
GD
Laboratory of Structural Biology, National Institute of Diabetes, Digestive, and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892.
Pangburn
M K
MK
Ginsburg
V
V
D000595:Amino Acid Sequence; D003165:Complement System Proteins / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000494:pharmacology; D011414:Properdin / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D012689:Sequence Homology, Nucleic Acid; D013433:Sulfoglycosphingolipids / Q000378:metabolism*; D019699:Thrombospondins
D006028:Glycosphingolipids; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D013433:Sulfoglycosphingolipids; D019699:Thrombospondins; D011414:Properdin; D003165:Complement System Proteins